Odochi O Chukwu^{1, 2, 3} , Anthony C Ezimah², Albert E Okorocha², Grace Ottah-Umahi⁴, Gertrude N Onyeji⁵, Cordilia O Iyare¹, Ofovwe O Ekakitie⁶, Nnaemeka T Asogwa⁷

Abstract

Purpose: To evaluate the docking of Moringa oleifera Lam. (Moringaceae) leaf extract (MoLE) phytochemicals to estrogen receptor-beta (ER-β) and assess its neuroprotective effect on the hippocampus and amygdala in pregnant rats under chronic unpredictable stress (CUS). Methods: Thirty healthy virgin female Albino-Wistar rats were randomly assigned to six groups (n = 5 per group). Pregnancy was confirmed and treatments were administered orally via gavage from gestational day (GD) 8 to GD 21. Group I (Normal Control) received only water and chow; Group II (CUS Control) was exposed to CUS without treatment; Group III (MoLE Low Dose) received 5 mg/kg/day of aqueous MoLE; Group IV (MoLE High Dose) received 10 mg/kg/day of methanol MoLE; Group V (CUS + MoLE Low Dose) received CUS + 5 mg/kg/day MoLE; and Group VI (CUS + MoLE High Dose) received CUS + 10 mg/kg/day MoLE. At the end of two weeks, histological assessments of the hippocampus and amygdala were conducted to evaluate tissue integrity. Results: Molecular docking revealed that 1-Propanol, 3,3'-oxy bis and 1,2,3-Trimethyldiaziridine were the most potent ligands for ER-β among the MoLE phytoconstituents. Histological examination showed severe neuronal damage in the hippocampus and amygdala of the CUS Control group compared to Normal Control. MoLE treatment significantly reduced neurodegeneration, especially in the CUS + MoLE High Dose group (p < 0.05 vs CUS Control). This neuroprotective effect was dose-dependent and most evident in groups receiving both CUS and MoLE (Groups V and VI). Conclusion: Orally administered MoLE during mid-to-late pregnancy reduces stress-induced neuronal damage, highlighting its potential as a neuroprotective agent. Further studies should isolate and characterize its active compounds.